Cell-Cell communication between skinkeratinocytes and fibroblats is non-redundantly coded through inflammatory cytokines

Cell-cell communication between keratinocytes and fibroblasts is essential for skin homeostasis, regulation, and regeneration. How extracellular cytokine signaling, intracellular protein signaling and transcriptional regulation initiate and maintain this communication is still largely unknown. Here, we study in vitro the secretome and transcriptome dynamics that establish double paracrine cell-cell communication between normal human keratinocytes (NHK) and human dermal fibroblasts (HDF). To mimic double paracrine stimulation, we stimulate HDF with NHK-conditioned medium for 18 hours and use the then HDF-conditioned medium to stimulate the NHK. The NHK response is quantified at different timepoints for a duration of up to 24 hours. We find that double paracrine stimulation changes extracellular matrix composition and activates translation and enhances keratinocyte migration. The response of NHK to double paracrine communication with human dermal fibroblasts were recorded at t=[ 1,2,4,6,12,24] hours after stimulation. Unstimulated control time points were taken at t=[ 0,4,12] hours.